Ocrelizumab for the treatment of multiple sclerosis: Safety, efficacy, and pharmacology

Abstract

The success of selective B-cells depleting therapies, as the anti-CD20 antibodies, in patients with multiple sclerosis (MS) has confirmed that B-cells are critical in the immune pathogenesis of the disease. Ocrelizumab, a humanized monoclonal antibody that selectively targets CD20+ B-cells, profoundly suppresses acute inflammatory disease activity, represent-ing a highly effective therapy for relapsing-remitting multiple sclerosis (RRMS). It is also the first proven therapy able to slow disability progression in primary progressive multiple sclerosis (PPMS), particularly in patients with signs of acute radiological activity before being enrolled. Effectiveness has widely been demonstrated in randomized clinical trials (RCTs), and recently confirmed in open-label extension trials. Here, we review the role of B-cells in MS, the mechanism of action of ocrelizumab, its pharmacokinetics and pharma-codynamics, and the clinical data supporting its use, as well as safety data. We focus on issues related to the maintenance of immunocompetence, essential to ensure an immune response to either a primary infection or a vaccination. Lastly, we discuss about the possible role of ocrelizumab as an exit strategy from natalizumab-treated patients at risk of develop-ing multifocal progressive leukoencephalopathy. In view of using ocrelizumab chronically, collecting long-term safety data and finding strategies to minimize adverse events will be extremely relevant.